The goal of this project is to learn more about the control of movement in normal humans and in patients with voluntary movement disorders such as Parkinson's disease, dystonia, cerebellar ataxia, and hemiplegia from stroke. The tools we use include clinical neurophysiological methods such as electroencephalography, electromyography, and transcranial magnetic stimulation (TMS) and neuroimaging with positron emission tomography and functional magnetic resonance imaging (fMRI). Currently active projects in the Section include studies of normal physiology, the pathophysiology and treatment of dystonia, the bradykinesia in Parkinson?s disease, and recovery from hemiplegia. We are trying to determine EEG methods to predict in real time when someone is going to move and whether they will move their right or left hand. We have optimized features and classification methods for the prediction. Our real-time study demonstrated that we can reliably predict human movement intention before movement occurs. We are now attempting to reduce missed-predictions and explore methods to predict laterality of movement intention. The work should be relevant for use with a brain-computer interface. Simple movements have been studied for many years, but most movements humans make are more complex. We have been studying complex praxis movements with both EEG and fMRI. fMRI shows a pattern of parietal and premotor activity, more in the left hemisphere regardless of the hand used for making the movement. Coherence analysis with EEG has shown that parietal and premotor areas are coherent during preparation and execution of movement, inferring event related functional connectivity. Using event-related fMRI we assessed hemispheric lateralization of transitive (tool-related) and intransitive (communicative) praxis movements in normal people and patients with ideomotor apraxia. The findings of this study point to left hemispheric organization of normal praxis movements. Preliminary findings from two patients with IMA suggest that impaired praxis movements are associated with an altered pattern of lateralization, particularly if the disorder is more severe. We have been doing many studies of dystonia largely in patients with focal hand dystonia. We have devoted considerable time in pursuing the hypothesis that there is a deficient surround inhibition with voluntary movement in dystonic patients. We have demonstrated this with TMS. We are now pursuing the mechanism of surround inhibition studying different types of known inhibitory processes. We are also using EEG methods to see if this will help reveal surround inhibition mechanisms. In another effort to identify EEG evidence of deficient intracortical inhibition in focal hand dystonia, we recorded scalp somatosensory evoked potentials from median nerve electric stimulation to quantify high frequency oscillations, which may reflect the activity of inhibitory interneurons in the cortex. We have been studying the electrophysiological correlate of the deficit in somesthetic discrimination in focal hand dystonia. We are also studying the blink reflex in patients with blepharospasm and torticollis. In this study, we are evaluating the R3 component of the blink reflex and comparing it with first degree unaffected relatives and control subjects. We are interested to see if there is a possible neurophysiological marker in the unaffected first degree relatives. We are currently exploring the genetics of movement disorders with several different populations of patients. We have evaluated approximately 250 patients with focal dystonia (blepharospasm, torticollis, writer's cramp, Meige's Syndrome and spasmodic dysphonia). This collection includes families where focal dystonia is present, as well as, sporadic cases. In addition, we are also looking into the genetics of essential tremor through a large family (40 people) with multiple members affected. Both studies are aimed at identifying the gene or genes responsible for the specific movement disorder. In the area of Parkinson's Disease, we are evaluating the efficacy of various types of non-invasive brain stimulation. High frequency repetitive TMS lead to improvement in the speed of gait and hand movements in patients with Parkinson?s Disease in a placebo controlled trial. We are now studying transcranial direct current stimulation. We are also studying postural instability and its changes with aging, given the importance of falls in the elderly. We are pursuing the hypothesis that neural detectors of unstable postures deteriorate with aging. We have evidence for these neural detectors with both EEG and fMRI studies. Along this line of research of postural stability, we are also evaluating the role of vision in postural control using virtual reality (VR). In studies of hemiplegia, we are studying the physiology of diaschisis. We have confirmed the feasibility of a magnetic resonance spectroscopy technique for analysis of GABA and are applying this now to patients with subcortical stroke. We are also assessing the safety of using high frequency repetitive TMS in patients with stroke, hoping that this will be a useful adjunct to physical therapy.